Background: There is considerable awareness in the literature on the burden of caring for patients with chronic illnesses. However there is a paucity of reports on the burden of care on informal caregivers of patients with disorders of psychoactive drug use in Nigeria. Aim: This study aimed at determining the burden of care experienced by informal caregivers of patients with disorders of psychoactive drug use and compared this with the burden of informal caregivers of patients with cancer. Methods: Using a cross-sectional design, 89 consecutively recruited informal caregivers of patients admitted for the treatment of alcohol and or cannabis dependence with or without psychotic features at The Psychiatric hospital Yaba (study group) and cancer patients admitted at The Lagos University Teaching Hospital Idi-Araba (control group) were recruited for the study. The participants were matched for age, gender and educational attainment. The WHO ICD-10 criteria research version was used to establish the diagnosis of mental and behavioural disorder due to psychoactive drug use in the patients at the Psychiatric hospital while a socio- demographic questionnaire and Zarit burden interview questionnaire were administered to all the informal caregivers who satisfied the inclusion criteria for the study which took place over a six month period. Results: Significantly more caregivers in the study group were parents, siblings or offsprings of the patients (p < 0.001). The caregiving duration was longer in the study group (p <0.001) while monthly costs and available support for the caregiver were significantly lower in the study group (p <0.001 and p=0.022 respectively) compared with the control group. High burden was reported by significantly more informal caregivers in the study group than in the control group (p<0.001). In the study group higher mean burden score was found to be associated with residing in the urban area (p=0.035) and being semiskilled or unskilled (p=0.001). It was also associated with lack of external support for the participant (p=0.013) and a caregiving duration of more than 5 years (p=0.006). In the control group significantly higher mean burden score was associated with residing in urban areas. Compared with the control group, high burden was found among more participants who were semi skilled or unskilled and who lacked external support in the study group (p=0.018 and 0.025 respectively). Also more participants who were parents, siblings or off springs to the patient and who had been providing care for more than 5 years in the study group experienced high burden compared with the control group. This difference was significant (p<0.001 and <0.001 respectively). Predictors of burden were the non availability of support (p=0.049), duration of caregiving (p=0.003) and the relationship between the caregiver and the patient (p=0.024). Conclusion: Informal caregivers of patients with disorders of psychoactive drug experienced high levels of burden when compared with informal caregivers of patients with cancer. Measures need to be put in place to care for this group of caregivers to enable them carry out their caregiving role effectively